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EP3216782B1 - Composés d'acides aminés de fer, procédé de préparation de composés d'acides aminés de fer, compositions contenant des composés d'acides aminés de fer et leurs utilisations - Google Patents

Composés d'acides aminés de fer, procédé de préparation de composés d'acides aminés de fer, compositions contenant des composés d'acides aminés de fer et leurs utilisations Download PDF

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Publication number
EP3216782B1
EP3216782B1 EP15856332.0A EP15856332A EP3216782B1 EP 3216782 B1 EP3216782 B1 EP 3216782B1 EP 15856332 A EP15856332 A EP 15856332A EP 3216782 B1 EP3216782 B1 EP 3216782B1
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Prior art keywords
iron
ferric
ferrous
amino acid
sodium
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EP3216782A4 (fr
EP3216782A1 (fr
Inventor
Ricardo Da Silva Sercheli
Nelson Henriques FERNANDES
Nelson Henriques Fernandes Filho
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Npa - Nucleo De Pesquisas Aplicadas Ltda
NPA Nucleo de Pesquisas Aplicadas Ltda
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Npa - Nucleo De Pesquisas Aplicadas Ltda
NPA Nucleo de Pesquisas Aplicadas Ltda
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/76—Metal complexes of amino carboxylic acids
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING OR TREATMENT THEREOF
    • A23C9/00—Milk preparations; Milk powder or milk powder preparations
    • A23C9/12—Fermented milk preparations; Treatment using microorganisms or enzymes
    • A23C9/13—Fermented milk preparations; Treatment using microorganisms or enzymes using additives
    • A23C9/1322—Inorganic compounds; Minerals, including organic salts thereof, oligo-elements; Amino-acids, peptides, protein-hydrolysates or derivatives; Nucleic acids or derivatives; Yeast extract or autolysate; Vitamins; Antibiotics; Bacteriocins
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING OR TREATMENT THEREOF
    • A23C9/00—Milk preparations; Milk powder or milk powder preparations
    • A23C9/152—Milk preparations; Milk powder or milk powder preparations containing additives
    • A23C9/1526—Amino acids; Peptides; Protein hydrolysates; Nucleic acids; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
    • A23G3/00—Sweetmeats; Confectionery; Marzipan; Coated or filled products
    • A23G3/34—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof
    • A23G3/36—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof characterised by the composition containing organic or inorganic compounds
    • A23G3/44—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof characterised by the composition containing organic or inorganic compounds containing peptides or proteins
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Preparation or treatment thereof
    • A23L2/52—Adding ingredients
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/16—Inorganic salts, minerals or trace elements
    • A23L33/165—Complexes or chelates
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/175—Amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/28—Compounds containing heavy metals
    • A61K31/295—Iron group metal compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/02—Nutrients, e.g. vitamins, minerals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/06—Antianaemics
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C229/06—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton
    • C07C229/08—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to hydrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C229/24—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having more than one carboxyl group bound to the carbon skeleton, e.g. aspartic acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C321/00—Thiols, sulfides, hydropolysulfides or polysulfides
    • C07C321/12—Sulfides, hydropolysulfides, or polysulfides having thio groups bound to acyclic carbon atoms
    • C07C321/14—Sulfides, hydropolysulfides, or polysulfides having thio groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C59/01—Saturated compounds having only one carboxyl group and containing hydroxy or O-metal groups
    • C07C59/08—Lactic acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C59/235—Saturated compounds containing more than one carboxyl group
    • C07C59/245—Saturated compounds containing more than one carboxyl group containing hydroxy or O-metal groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C59/235—Saturated compounds containing more than one carboxyl group
    • C07C59/245—Saturated compounds containing more than one carboxyl group containing hydroxy or O-metal groups
    • C07C59/255—Tartaric acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C59/235—Saturated compounds containing more than one carboxyl group
    • C07C59/245—Saturated compounds containing more than one carboxyl group containing hydroxy or O-metal groups
    • C07C59/265—Citric acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the present invention relates to the field of chemistry and more specifically to the field of chemistry applied to iron complexes of water soluble amino acids, processes for preparing these complexes, the use of the complexes as a way of supplementation for the prevention or treatment of iron deficiency anemia in humans or animals, and food or pharmaceutical compositions containing them.
  • Iron deficiency is one of the most common causes of anemia and may be the most frequent nutritional deficiency in the world, affecting a significant portion of the world population. Iron deficiency is mainly caused by the lack of this mineral in the diet or low iron absorption in the body and, in addition to contributing to anemia, also alters other physiological conditions.
  • iron deficiency can be even more pronounced during growth, pregnancy and menstruation, and affect up to seven times more women than males. For these reasons, it is currently very common to use iron supplements for fortification of processed foods or as components for preparing pharmaceutical or food compositions, alone or in combination with other nutrients.
  • iron there are several compounds presently available for the supplementation of iron that can be selected from inorganic or organic forms such as pyrophosphates, sulfates, sugars or polysaccharide complexes, gluconates, citrates, and amino acid chelates, among others.
  • inorganic or organic forms such as pyrophosphates, sulfates, sugars or polysaccharide complexes, gluconates, citrates, and amino acid chelates, among others.
  • these compounds can result in changes in the organoleptic properties of the processed food or in unwanted interactions with other components of formulations containing them, limiting the use of these forms of iron in desired applications.
  • iron is perhaps the nutrient that offers most challenges for the preparation of food or pharmaceutical compositions, as it normally results in the appearance of undesirable flavors and coloring when incorporated into processed foods or medicines and causes decomposition of other components present in the pharmaceutical formulations, such as vitamins.
  • the forms of iron which are commercially available can be classified into two groups: (i) iron forms which show high solubility and, consequently, higher bioavailability and lower stability in formulations, and (ii) iron forms that exhibit low solubility and, consequently, lower bioavailability and increased stability in formulations.
  • iron forms which show high solubility and, consequently, higher bioavailability and lower stability in formulations and iron forms that exhibit low solubility and, consequently, lower bioavailability and increased stability in formulations.
  • WO03/016332 describes ferric trisglycinate with citric acid as chelate for mineral nutrition.
  • the iron amino acid compound described therein does not comprise iron hydroxide or a cation.
  • iron carbohydrate complexes Other forms of iron used for nutritional or therapeutic purposes are prepared from saccharides or drivatives thereof and are referred to as iron carbohydrate complexes.
  • Compounds of this class include oxides and hydroxides of iron(III) (iron oxyhydroxides) coordinated with polyhydroxy compounds such as dextran, polymaltose, sucrose, gluconic acid, among others, with or without the sodium ion present in their structure.
  • Such substances are characterized in that they are in the form of a plurality of iron(III) complexes or agglomerates associated to the formation of macromolecules that may have an average molecular weight distribution of up to 600 kDa.
  • oxides and hydroxides of iron(III) are stabilized by carbohydrates which keep the iron species in solution.
  • Type I complexes include iron dextran and iron dextrin and are known to cause anaphylactic reactions during treatments.
  • Type II complexes include compounds of intermediate stability and strength, such as iron saccharate, which have low solubility.
  • Type III complexes comprise labile and weak iron compounds, such as iron (III) gluconate, iron(III) citrate and iron(III) sorbitol.
  • Type IV complexes comprise mixtures of at least two complexes of different classes and, considering their iron distribution patterns, none can be considered clinically safe. In such cases, toxic reactions might be expected even at lower therapeutic doses and, thus, intravenous use is not recommended.
  • the processes are characterized by the formation of possibly toxic by-products and the need for use of difficult-to-handle and obviously hazardousness reagents, such as bromine derivatives and activated chlorine salts.
  • hazardousness reagents such as bromine derivatives and activated chlorine salts.
  • the undesired combination of several steps, such as hydrolysis and reduction of saccharides, is required in addition to ultrafiltration for the isolation of products in certain molecular weight ranges.
  • Fe(III) saccharate is classified as a compound with very low solubility in water and is related to ferrous fumarate and ferrous succinate, compounds known to be insoluble in food formulations, as verified in R.F. Hurrell, Preventing Iron Deficiency Through Food fortification, Nutrition Reviews, 55, 1997, 210-222 .
  • iron administration in the form of Fe(III) saccharate by carriers selected from liquid food formulations such as drinks, syrups, juices, milk, dairy compositions and yogurt, among others is disadvantageous.
  • iron supplementation is preferentially made with soluble iron compounds, which causes an undesirable organoleptic alteration in the products and, mainly, changes in taste and color.
  • ferrous sulfate, ferrous lactate, ferrous gluconate and ferric ammonium citrate as well as the less soluble forms ferrous fumarate and ferric citrate produce undesired coloration when added to chocolate milk drinks.
  • Taste changes may be directly related to the metallic taste of iron inherent in the commercially available forms, particularly in beverages, but may also be caused by the oxidation of fats present in food compositions in iron catalyzed reactions, occurring during the storage period of the food, which reduces its shelf life.
  • the present invention relates to iron compounds with excellent palatability that also have high solubility and stability. More particularly such compounds comprise iron oxyhydroxides coordinated with ligands which are selected solely between essential and nonessential amino acids, organic acids and their salts.
  • a second embodiment of the present invention is the procedure for obtaining such compounds.
  • a third embodiment of the present invention relates to pharmaceutical and / or food compositions comprising the iron compound hereby obtained.
  • the present invention relates to such compounds and / or compositions for use as a medicine, a drug or a nutritional supplement, advantageously for preventing and / or treating iron deficiencies in humans and animals.
  • the present invention relates to iron compounds as defined in appended claims 1 or 2 with excellent palatability and that also have high solubility and stability.
  • Such compounds include Fe(III) oxyhydroxides coordinated with ligands.
  • the compounds formed comprising essential or non-essential amino acids and carboxylic acids, ionized or not, are coordinated by various interactions with iron oxyhydroxides.
  • iron amino acid complexes For a better understanding of the invention only, such compounds may also be referred to herein as iron amino acid complexes.
  • the iron complexes of amino acids described in this invention differ totally from substances comprising complexes of iron(III) oxyhydroxides so far known in the art.
  • the compounds described herein are not prepared with or contain in their composition carbohydrates or any of their derivatives. More specifically, the compounds of the present invention are not prepared with or contain substances classified as saccharides or activated or non-activated polysaccharides, such as dextrans, dextrins, dextrose, polydextrose, maltitol, maltose, glucose, sucrose, sorbitol, gluconic acid, amino saccharides or similar substances.
  • the iron amino acid complexes described in this invention are completely different from the substances comprising the amino acid chelates, which are a class of compounds characterized by structurally presenting a metal center coordinated to amino acids.
  • iron occurs in the form of its possible oxyhydroxides, obtaining, thus, particular chemical structures that show different and absolutely unexpected properties for iron containing amino acid complexes.
  • the compounds of the present invention comprise a new class of substances and have the necessary characteristics to be used as ingredients for preparing compositions for hematinic iron administration in humans and animals.
  • the excellent solubility of the compounds of the present invention provide that the iron complexes of amino acids can be administered in liquid carriers such as beverages, milk, ferments or syrups, without changes observed to the organoleptic properties of foods, especially in color and flavor.
  • iron complexes described in this invention also circumvents the problems associated with the addition of iron in compositions prepared with color additives normally used for the preparation of pharmaceutical and food formulations, since it does not interact with these substances and, thus, does not cause changes in anticipated and desired colorations.
  • the use of the complexes of interest of this invention also circumvents the problems associated with the addition of iron in compositions containing sensitive nutrients to commercially available sources of iron.
  • compositions containing vitamins, omega-3, omega-6, omega-9 and other components of naturally occurring oils and their derivatives are more susceptible to decomposition in the presence of iron.
  • iron complexes herein disclosed does not cause the reduction of nutrient contents in the formulations containing them.
  • Another object of the invention comprises a process for obtaining the compounds of the present invention.
  • Another object of the invention refers to pharmaceutical and / or food compositions comprising as the main active ingredient the compounds of interest of this invention, iron(III) amino acid complexes and at least one pharmaceutically and / or nutritionally acceptable carrier.
  • Another object of the invention relates to the iron(III) amino acid complexes as mineral and / or composition forms comprising the same, for use as a medicine, a drug or a nutritional supplement, advantageously for preventing and / or treating iron deficiencies in humans and animals.
  • interactions with iron(III) species occur both through the carboxylic and amino groups of the amino acids, and through the carboxylic or hydroxyl groups of the organic acids, and the coordination of the organic ligands can occur through only one, or more than one binding site, leading to the formation of cyclic structures with the iron(III) species.
  • the compounds of the present invention are represented by Formula I.
  • the organic acid selected is citric acid and in another preferred embodiment of the present invention when R 1 and R 4 are not a substituent and R 2 and R 3 are the same as -H, the organic acid selected is fumaric acid.
  • the compounds of the present invention are also represented as consisting of iron(III) amino acid complexes comprising from 0.01 to 30% w / w iron in the form of their possible hydroxides, and preferably from 0.5 to 20% w/w of iron, 0.1 to 99% of an amino acid, and preferably of 5.0 to 90.0% of an amino acid, 0.01 to 99% of an organic acid, and preferably 1.0 to 50% of an organic acid and 0.001 to 40% of a cation, with water contents ranging from 0.0 to 99% and preferably ranging from 0.1 to 20%.
  • Organic acids are selected from citric, oxalic, tartaric, malic, succinic, adipic, lactic, glycolic, ascorbic, acetic, salicylic, fumaric, maleic, malonic, pectin, pectin hydrolysates or mixtures thereof.
  • the selected organic acid is citric acid.
  • the cations are selected from sodium, potassium, calcium, magnesium and ammonium, and preferably sodium.
  • the selected iron source is Fe(II) form
  • one of the various methods of conversion from Fe(II) to Fe(III) available in the prior art should be carried out before or during the reaction between the iron and the amino acid and the selected organic acid, so that the Fe(II) contents in the reaction medium are substantially zero or insignificant, such as Fe(II) contents of less than 0.1%, as compared to total iron content.
  • the selected base refers to sources of sodium, potassium, calcium, magnesium and ammonium and, preferably, sodium.
  • step (i) occurs at a temperature in the range of 20 to 100°C and in the presence of a base at varying pH ranges between 2.0 and 14.0, and preferably between 3.0 and 11.0.
  • the development time of the reaction for preparing the amino acid complex may range between 10 min and 24 hours, depending on the iron source, amino acid, organic acid or base selected.
  • the stoichiometric ratio used between iron and the selected amino acid is not less than 1:0.05 and preferably is not greater than 1:100, respectively. More preferably, the stoichiometric ratio between iron and the selected organic acid may range between 1:0.01 and 1:50 and preferably, range between 1:0,1 and 1:10.
  • the base is most preferably selected from potassium hydroxide, sodium hydroxide, calcium oxide, calcium hydroxide, calcium carbonate, potassium carbonate, potassium bicarbonate, sodium carbonate, sodium bicarbonate, potassium phosphate or calcium alkali, magnesium oxide, magnesium hydroxide, magnesium carbonate, ammonium hydroxide, or any one of their combinations.
  • the separation can be done by ultrafiltration processes, nanofiltration or dialysis of the reaction medium and subsequent concentration by evaporation until a solution is obtained with the concentration of the desired complex.
  • separation may be made by filtering processes.
  • the separation can be made by adding a solvent in the reaction medium in which the complex of interest shows low solubility, such as ethanol.
  • the drying can be made by processes such as drying under reduced pressure in rotary dryers, in greenhouses with or without ventilation, spray dryer, flash dryer, among others.
  • the characterization of the compounds herein obtained by the process of the present invention was performed by spectroscopic analysis in the infrared region.
  • the iron(III) amino acid complexes obtained by the process of the present invention show polymorphic phases that are characteristics of iron oxyhydroxides, also namely iron hydroxide, such as goethite (a-FeOOH) and no formation of maghemite ( ⁇ -Fe2O3) or magnetite (Fe3O4) is observed.
  • Another aspect of the invention relates to pharmaceutical and / or food compositions comprising the iron amino acid complexes as an active ingredient and at least one pharmaceutically and / or nutritionally acceptable carrier.
  • compositions disclosed by the present invention comprise about 0.01 to 200 mg iron / g of composition, 0.0 to 99% of a nutrient, 0.001 to 99% of a pharmaceutically or nutritionally acceptable inert carrier added in sufficient amounts to achieve the desired iron concentrations, 0.0 to 99% sweetener, 0.001 to 20% flavoring agents, 0.001 to 1% colors additives and 0.0 to 20%, and preferably 0.01 to 5% of at least one additive selected from desiccants, moisturizers, antioxidants, thickeners, stabilizers, sequestrants, lubricants, preservatives and acidity regulators or combinations thereof.
  • compositions of the present invention as presented in liquid form, comprise iron oxyhydroxides in colloidal form, commonly referred to as iron hydroxides, stabilized exclusively by amino acids, organic acids and their salts in the form of at least one of the iron amino acids complexes described in this invention in amounts that provide concentrations of 0.001 to 20% and preferably, of 0.01 to 10% of Fe(III).
  • compositions in the form of aqueous solutions do not present precipitates, even after storage periods of more than 2 years, and contain iron in high concentrations, which enable their commercial use exclusively in the form of their possible hydroxides, substances admittedly insoluble.
  • the liquid pharmaceutical and food compositions comprise iron(III) hydroxides in amounts providing from 0.01 to 12% of Fe(III), 0.01 to 30% of an organic acid, 0.5 to 70% of an amino acid, 0.0001 to 25% of a cation and 40 to 99.9% of water.
  • the food and / or pharmaceutical compositions may contain 0.001 to 99% of a nutrient, 0.001 to 99% of sweetener, 0.001 to 20% of flavoring agents, 0.001 to 1% of colors additives and 0.001 to 20% of at least one additive selected from desiccants, wetting agents, antioxidants, thickeners, stabilizers, sequestrants, lubricants, preservatives, acidity regulators or combinations thereof, colors additivess, sweeteners and flavorings.
  • a nutrient 0.001 to 99% of sweetener, 0.001 to 20% of flavoring agents, 0.001 to 1% of colors additives and 0.001 to 20% of at least one additive selected from desiccants, wetting agents, antioxidants, thickeners, stabilizers, sequestrants, lubricants, preservatives, acidity regulators or combinations thereof, colors additivess, sweeteners and flavorings.
  • suitable liquid carriers for preparing the compositions include, without limitation, water or mixtures of water and another carrier selected from sorbitol, xylitol, glucose, vegetable oils and their derivatives, aqueous solutions containing gums, sucrose, among other saccharides, alcohol, propylene glycol and the like in any proportion, provided that they enable the preparation of solutions of the iron amino acid complexes which may be administered orally, maintaining the indicated iron concentration limits.
  • selected inert carriers include, without limitation, compositions in the form of mixtures for puddings, cake mix, bread, cereals, soups, sauces, cereal bars, chewy candies, hard candies, chewing gums, cheeses, cream cheese, jellies, yogurts, fruit concentrates for the preparation of juices, yoghurts and dairy drinks, syrups, carbonated and noncarbonated beverages selected from soft drinks, juices, flavored waters, nectar like beverages , mixed drinks, milk drinks, powder mixes for the preparation of beverages, hot drinks like tea and coffee or others obtained by fermentation.
  • ingredients used for preparing the compositions described above include, without limitation, glucose, sucrose, xylitol, fructose, sorbitol, other mixtures of saccharides, salt, milk and products obtained from their processing such as caseins, caseinates, whey concentrates, whey isolates, among others, water, vegetable oils, vegetable proteins, animal proteins, yeast proteins, yeast extracts, ferments, fresh fruits, processed fruits, fruit extracts, fresh vegetables, processed vegetables, vegetable extracts, vegetable powders, flour, starches, eggs and products obtained from their processing, cereals, chocolate, cocoa, and any one of their mixtures, as well as colors additivess, flavors and enzymes in any proportions.
  • Examples of nutrients that may be present in the food and pharmaceutical compositions include, without limitation, minerals, vitamins, omega 3, omega 6, omega 9 vegetable oils or their derivatives, lycopene, lutein, carnitine, creatine, plant extracts, amino acids, peptides, proteins, among other nutritionally important substances.
  • Examples of minerals include zinc, calcium, magnesium, phosphorus, potassium, selenium, chromium, copper, manganese, cobalt, molybdenum, iodine, germanium, and mixtures thereof.
  • Examples of vitamins include Vitamins C, A, D, E, vitamins of B complex, vitamin K, folic acid, and mixtures thereof.
  • desiccants include, without limitation, calcium carbonate, microcrystalline cellulose, fatty acid salts (Ca, Na, K and NH4), sodium carbonate, sodium bicarbonate, sodium acid carbonate, magnesium carbonate, magnesium hydroxide, magnesium oxide, amorphous silicon dioxide, silica, calcium silicate, magnesium silicate, talc, sodium and aluminum silicate, aluminum sodium silicate, aluminum silicate and the like.
  • moisturizers include, without limitation, sodium lactate, potassium lactate, sorbitol and sorbitol syrup, mannitol, glycerol, glycerin, xylitol, polydextrose and the like.
  • antioxidants include, without limitation, ascorbic acid, sodium ascorbate, calcium ascorbate, potassium ascorbate, erythorbic acid, isoascorbic acid, sodium erythorbate, sodium isoascorbate, lecithins, sodium lactate, citric acid, calcium citrate, tri-calcium citrate, esters of citric acid and fatty acids with glycerol, esters of citric acid and mono and diglycerides, and the like.
  • stabilizers include, without limitation, sodium caseinate, gelatin, calcium carbonate, calcium acetate, lecithin, monosodium citrate, disodium citrate, sodium citrate, trisodium citrate, potassium citrate, tripotassium citrate , calcium citrate, tricalcium citrate, alginic acid, sodium alginate, potassium alginate, ammonium alginate, calcium alginate, agar, carrageenan and its salts, jata ⁇ gum, locust bean, guar gum, tragacanth gum, gum arabic, acacia gum, xanthan gum, karaya gum, gellan gum, mannitol, konjac gum, pectin, amidated pectin, microcrystalline cellulose, methylcellulose, hydroxypropylcellulose, methylethylcellulose, sodium carboxymethylcellulose, fatty acid salts (Ca, Na, K and NH4), mono and diglycerides of fatty acids, mono esters and diglycer
  • lubricants include, without limitation, colloidal silicas and the like.
  • preservatives include, without limitation, alkyl parabens such as methylparaben, propylparaben, acetic acid, calcium acetate, propionic acid, sodium propionate, calcium propionate, potassium propionate, sodium erythorbate, sodium isoascorbate, sodium benzoate and the like.
  • alkyl parabens such as methylparaben, propylparaben, acetic acid, calcium acetate, propionic acid, sodium propionate, calcium propionate, potassium propionate, sodium erythorbate, sodium isoascorbate, sodium benzoate and the like.
  • acidity regulators which may be used in order to maintain the food or pharmaceutical compositions in ranges of pH values ranging from 2.0 to 14.0 and preferably between 3.0 and 11.0 and include, without limitation, calcium carbonate, acetic acid, calcium acetate, lactic acid, malic acid, fumaric acid, sodium lactate, potassium lactate, calcium lactate, citric acid, monosodium citrate, disodium citrate, sodium citrate, tri-sodium citrate, potassium citrate, tri-potassium citrate, citrate of calcium carbonate, tri-calcium citrate, sodium carbonate, sodium bicarbonate, sodium carbonate, potassium carbonate, ammonium carbonate, ammonium bicarbonate, ammonium acid carbonate, magnesium carbonate, potassium sulfate, sodium hydroxide, potassium hydroxide, calcium hydroxide, ammonium hydroxide, magnesium hydroxide, calcium oxide, gluconic acid, glucono delta lactone, calcium gluconate and the like.
  • sweeteners include, without limitation, sucralose, aspartame, acesulfame potassium, sodium saccharin, cyclamate, thaumatin, steviosides, rebaudiosides, neohesperidin dihydrochalcone, alitame or mixtures thereof in any proportions.
  • the pharmaceutical and food compositions may comprise at least one iron(III) amino acid complex in combination with a second iron source.
  • the second iron source provides about 0.01 to 200 mg Fe / g of composition and iron from the iron(III) amino acid complex corresponds to about 0.1 to 99.9% of the total iron present in the composition.
  • suitable iron sources for the preparation of compositions in combination with the iron(III) amino acid complexes include, without limitation, ferrous citrate, ferric citrate, ferrous tartrate, ferric tartrate, iron and sodium citrates and tartrates, ferric hypophosphite, ferric albuminate, ferric chloride, ferrous chloride, ferric sulfate, ferrous sulfate, ammonium ferric sulfate, ammonium ferrous sulfate, ferric citrate, ferrous gluconate, ferrous iodide, ferrous lactate, ferrous fumarate, ferric triglycinate, ferrous bisglycinate, ferrous aspartate glycerate, ferric nitrate, ferric aspartate, ferric hydroxide, ferrous hydroxide, ferric hydroxide, ferrous oxide, metallic iron, ferric ascorbate, ferrous formate, ferrous acetate, ferrous malate, ferrous glutamate, iron g
  • Another embodiment of the present invention provides the use of iron(III) amino acid complexes of interest in the preparation of foods or drugs or as a nutritional additive for the prophylaxis and / or therapeutic and non-therapeutic treatment of iron deficiencies in humans and animals.
  • the iron(III) amino acid complexes are used in nutritionally effective amounts, and in general are preferably used in quantities not higher than the nutritional requirement of iron for the individuals to be supplemented, per dose of food or medicine.
  • iron requirements can vary from 5 to 1000 mg Fe / dose and in the case of food, doses may vary from 0.01 to 20 mg Fe / dose.
  • iron requirements may vary from 1 to 1000 mg Fe / dose or 1 to 1000 ppm Fe / kg feed.
  • dosage form of the composition of the present invention When the dosage form of the composition of the present invention is presented in solid form for administration through the oral route, such form may be coated or non-coated tablets, capsules, powders, granules or dragees.
  • the iron(III) amino acid complexes or the food and pharmaceutical compositions of the invention may be combined with a pharmaceutically acceptable inert carrier, such as lactose, calcium carbonate, starch, sucrose, glucose, cellulose derivatives, magnesium stearate, dicalcium phosphate, calcium sulfate, mannitol, sorbitol and the like.
  • a pharmaceutically acceptable inert carrier such as lactose, calcium carbonate, starch, sucrose, glucose, cellulose derivatives, magnesium stearate, dicalcium phosphate, calcium sulfate, mannitol, sorbitol and the like.
  • suitable binders, lubricants, disintegrating agents and coloring agents may also be incorporated into the blend.
  • Suitable binders include starch, gelatin, natural sugars such as glucose or beta-lactose, corn sweeteners, natural and synthetic gums such as acacia, tragacanth or sodium alginate, carboxymethylcellulose, polyethylene glycol, waxes and the like.
  • Lubricants that can be used in these dosage forms include sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride and the like.
  • Disintegrators include, without limitation, starch, cellulose derivatives, agar, bentonite, xanthan gum and the like.
  • compositions according to the present invention may also be administered in the form of liposome delivery systems or coupled to soluble or partially soluble polymers, as drug delivery carriers.
  • water a suitable oil
  • alcoholic solutions saline solution
  • aqueous fructose aqueous sorbitol
  • aqueous dextrose aqueous dextrose (glucose)
  • sugar solutions and glycols such as propylene glycol or polyethylene glycols and phosphate buffer are suitable carriers among others which may be selected for each particular use by those skilled in the art.
  • Hard candies containing the iron amino acid complex described in Example 1 are prepared by combining, cooking and hot molding of the components listed below in the following proportions: Component Content (%, w/w) Glucose syrup 65-55 Saccharose 31.9-43.5 Iron complex 0.1-0.05 Acidifier 0.5-0.2 Aroma and color 0.5-0.2 Water qsf
  • Syrups in the form of a liquid compositions are prepared by combining the following components, wherein the iron complex of Example 3 is initially dissolved in water: Component Content (%, w/w) Sorbitol 70% 25-35 Propylene glycol 30-50 Iron complex 0.1-0.05 Sequestrant 0.1-0.2 Thickener 0.1-0.5 Preservatives 0.1-0.2 Aroma and color 0.1-0.4 Water qsf
  • Food supplements in the form of preparations for powdered drinks are made by combining the following components in a Y-type mixer: Component Content (%, w/w) Calcium caseinate 40 - 45 Concentrated whey protein 8-16 Isolated soy protein 8-16 Sunflower oil 2-5 Iron complex 0.1-0.3 Fructose 20-30 Saccharose 10-20 Zinc bisglycinate 0.01-0.02 Aroma and color 0.2-0.5 Maltodextrin qsf
  • Beverages of fruit nectar type are prepared by combining the following components utilizing any of the iron complexes described in the previous Examples: Component Content (%, w/w) Fruit concentrate 10-20 Iron complex 0.01-0.25 Xanthan gum 0.2-0.5 Sucralose 0.5-1.0 Preservatives 0.1-0.2 Sequestrantes 0.01-0.03 Stabilizers 0.01-0.3 Acidifiers 0.5-1.0 Antioxidantes 0.05-0.2 Aroma and color 0.1-0.7 Water qsf
  • Suspensions in oral form are prepared by combining the following components utilizing any of the iron complexes described in the previous Examples: Component Content (%, w/w) Iron complex 0.1-0.05 Preservative 0.001-0.5 Thickener 10-0.01 Sweetener 1.0-0.01 Surfactants 10-0.01 Aroma and color 0.5-0.2 Antifoam 0.2-0.01 Solvent 1 80-1.0 Solvent 2 qsf
  • Chewable gums containing one of the iron amino acid complexes described in the previous Examples are prepared by combining, cooking and hot molding of the components listed below in the following proportions: Component Content (%, w/w) Glucose syrup 70-50 Xylitol 40-30 Iron complex 0.5-0.05 Acidifier 1.5-0.1 Preservative 0.2-0.01 Aroma and color 1.0-0.01 Water qsf
  • Preparations for powdered drinks are made by combining any of the iron amino acid complexes described in the previous Examples and the components listed below in a Y-type mixer: Component Content (%, w/w) Iron complex 1.0-0.5 Aroma 20-10 Color 1.5-0.5 Zinc oxide 0.5-0.1 Acidity Regulator 20-10 Acidifier 10-5 Premix of vitamin C, vitamin B3, vitamin B12, folic acid* 4.0-2.0 Carrier Qsf * Amount sufficient to reach 100% of the RDI of each component after dissolving the powder prepared in 200 ml of liquid.

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Claims (15)

  1. Composés d'acide aminé et de fer, de formule moléculaire
    Figure imgb0006
     dans laquelle :
    R est -H ou est la chaîne latérale d'un acide aminé essentiel ou non essentiel choisi parmi l'alanine, la phénylalanine, la leucine, l'isoleucine, la proline, l'hydroxyproline, l'arginine, la méthionine, l'acide aspartique, l'acide glutamique, la valine, la thréonine, l'isothréonine, l'histidine, le tryptophane, la sérine, la glutamine, l'un quelconque de leurs mélanges, et de préférence -H représentant l'acide aminé glycine ;
    R1 est -H ou -OH ;
    R2 est -H ou -CH2COOH ;
    R3 est -H ou -OH ;
    R4 est H ;
    k vaut 0 ou 1 ;
    si k vaut zéro, alors q peut varier entre 1 et 3 ;
    si k vaut un, alors q peut varier entre zéro et 3 ;
    X est -Na, -K, -Ca, -Mg ou -NH4 ;
    Y peut varier entre 0 et 20 ;
    le rapport molaire m/n est situé dans la plage comprise entre 1/0,05 et 1/100, avantageusement entre 1/0,5 et 1/10 ;
    le rapport molaire m/p est situé dans la plage comprise entre 1/0,01 et 1/50, avantageusement entre 1/0,1 et 1/1 ;
    le rapport molaire m/h est situé dans la plage comprise entre 1/0,0001 et 1/50, avantageusement entre 1/0,001 et 1/5.
  2. Composés d'acide aminé et de fer consistant en des complexes d'acide aminé et de fer(III) qui comprennent :
    0,01 à 30 % p/p de fer sous la forme de ses hydroxydes possibles, de préférence 0,5 à 20 % p/p de fer ;
    0,1 à 99 % d'un acide aminé, et de préférence entre 5,0 et 90,0 % d'un acide aminé,
    l'acide aminé étant choisi parmi la glycine, la L-lysine, la L-alanine, la L-phénylalanine, la L-leucine, la L-isoleucine, la L-proline, la L-hydroxyproline, la L-arginine, la L-ornithine, la L-méthionine, l'acide L-aspartique, l'acide L-glutamique, la L-valine, la L-thréonine, la L-isothréonine, la L-histidine, le L-tryptophane, la L-sérine, la L-glutamine, la L-citrulline, et leurs mélanges, et mêmes leurs formes énantiomorphes, et de préférence la glycine ;
    0,01 à 99 % d'un acide organique, et de préférence entre 1,0 et 50 % d'un acide organique,
    l'acide organique étant choisi parmi les acides citrique, oxalique, tartrique, malique, succinique, adipique, lactique, glycolique, ascorbique, acétique, salicylique, maléique, malonique, fumarique, la pectine, les hydrolysats de pectine, et leurs mélanges, et de préférence l'acide citrique ;
    0,001 à 40 % d'un cation,
    le cation étant choisi parmi le sodium, le potassium, le calcium, le magnésium, l'ammonium, l'une quelconque de leurs combinaisons, et de préférence le sodium.
  3. Composés d'acide aminé et de fer selon la revendication 1, dans lesquels la formule moléculaire
    Figure imgb0007
     représente des acides carboxyliques choisis parmi les acides citrique, tartrique, malique, succinique, adipique, fumarique, et de préférence l'acide citrique.
  4. Procédé pour obtenir des composés d'acide aminé et de fer de l'une quelconque des revendications 1 à 3, comprenant :
    (i) la réaction d'une source de fer(III) avec un acide aminé, un acide organique et une base en solution aqueuse, le temps de réaction étant avantageusement situé dans la plage allant de 10 minutes à 24 heures, en fonction de la source de fer, de l'acide aminé, de l'acide organique et de la base sélectionnés ;
    (ii) la séparation du complexe d'acide aminé et de fer(III) obtenu sous forme solide ou sous la forme d'une solution aqueuse, la séparation étant avantageusement effectuée par des procédés d'ultrafiltration, de nanofiltration ou de dialyse du mélange réactionnel et concentration subséquente par évaporation, jusqu'à ce qu'une solution ayant les concentrations de complexe souhaitées soit obtenue ; par l'intermédiaire d'un procédé de filtration ou par addition d'un solvant dans lequel le complexe de fer(III) est insoluble ; et
    (iii) le séchage du solvant utilisé pour l'obtention du complexe d'acide aminé et de fer(III), le séchage étant avantageusement effectué sous pression réduite dans des séchoirs rotatifs, dans des fours avec ou sans ventilation, des séchoirs par pulvérisation, ou des séchoirs pneumatiques.
  5. Procédé selon la revendication 4, dans lequel le rapport stœchiométrique entre la source de fer et l'acide aminé sélectionné n'est pas inférieur à 1/0,05, et de préférence pas supérieur à 1/100, respectivement, le rapport stœchiométrique entre la source de fer et l'acide organique sélectionné varie entre 1/0,01 et 1/50 et le rapport stœchiométrique entre la source de fer et la base varie entre 1/0,001 et 1/50.
  6. Procédé selon la revendication 4, dans lequel la source de fer est choisie parmi le citrate ferreux, le citrate ferrique, le tartrate ferreux, le tartrate ferrique, les citrates et tartrates de fer et de sodium, l'hypophosphite ferrique, l'albuminate ferrique, le chlorure ferrique, le chlorure ferreux, le sulfate ferrique, le sulfate ferreux, le sulfate d'ammonium ferrique, le sulfate d'ammonium ferreux, le citrate ferrique, le citrate d'ammonium ferrique, le gluconate ferreux, l'iodure ferreux, le lactate ferreux, le fumarate ferreux, le triglycinate ferrique, le bisglycinate ferreux, l'aspartate-glycinate ferreux, le nitrate ferrique, l'aspartate ferrique, le phosphate ferrique, l'hydroxyde ferreux, l'hydroxyde ferrique, l'oxyde ferreux, l'oxyde ferrique, le fer métallique, l'ascorbate ferrique, le formiate ferreux, l'acétate ferreux, le malate ferreux, le glutamate ferreux, le sulfate de glycine et de fer et le pyrophosphate ferrique soluble, le sous-sulfate ferrique, le citrate de sodium ferrique, l'édétate de sodium et de fer, le formiate ferrique, l'oxalate d'ammonium ferrique, l'oxalate de potassium ferrique, l'oxalate de sodium ferrique, le peptonate ferrique, et d'autres formes de fer, ainsi que leurs combinaisons respectives.
  7. Procédé selon la revendication 4, dans lequel l'acide aminé est choisi parmi la glycine, la L-lysine, la L-alanine, la L-phénylalanine, la L-leucine, la L-isoleucine, la L-proline, la L-hydroxyproline, la L-arginine, la L-ornithine, la L-méthionine, l'acide L-aspartique, l'acide L-glutamique, la L-valine, la L-thréonine, la L-isothréonine, la L-histidine, le L-tryptophane, la L-sérine, la L-glutamine, la L-citrulline, et aussi leurs mélanges et leurs formes énantiomorphes, et de préférence la glycine.
  8. Procédé selon la revendication 4, dans lequel l'acide organique est choisi parmi les acides citrique, oxalique, tartrique, malique, succinique, adipique, lactique, glycolique, ascorbique, acétique, salicylique, maléique, fumarique, malonique, la pectine, les hydrolysats de pectine, et leurs mélanges, et de préférence l'acide citrique.
  9. Procédé selon la revendication 4, dans lequel la base est choisie parmi l'hydroxyde de potassium, l'hydroxyde de sodium, l'oxyde de calcium, l'hydroxyde de calcium, le carbonate de calcium, le carbonate de potassium, le bicarbonate de potassium, le carbonate de sodium, le bicarbonate de sodium, les phosphates de potassium et les alcalis calciques, l'oxyde de magnésium, l'hydroxyde de magnésium, le carbonate de magnésium, l'hydroxyde d'ammonium, et l'une quelconque de leurs combinaisons.
  10. Compositions pharmaceutiques ou nutritionnelles, comprenant au moins un composé de la revendication 1 ou 2 et au moins un véhicule acceptable du point de vue pharmaceutique ou nutritionnel, le véhicule étant avantageusement choisi parmi les maltodextrines, l'amidon, le sulfate de calcium, le sulfate de magnésium, le carbonate de calcium, les dérivés de cellulose, le lactose et ses dérivés, l'eau, les mélanges d'eau et d'un autre véhicule choisi parmi les solutions de sorbitol, xylitol, glucose, saccharose, entre autres saccharides, l'alcool, le propylèneglycol, les mélanges pour crème dessert, les mélanges pour gâteau, les pains, les céréales, les soupes, les sauces, les barres de céréales, les bonbons à mâcher, les bonbons durs, la gomme à mâcher, les fromages, le caillé, les confitures, les yaourts, les concentrés de fruit pour la préparations de jus, les yaourts et boissons lactées, les sirops, les boissons gazeuses et non gazeuses choisies parmi les boissons sans alcool, les jus, les eaux aromatisées, les boissons de type nectar, les boissons mélangées, les boissons lactées, les mélanges en poudre pour la préparation de boissons, les préparations de poudre effervescente, la poudre de chocolat, les boissons chaudes telles que le thé ou le café ou d'autres obtenues par fermentation.
  11. Compositions selon la revendication 10, comprenant :
    0,01 à 200 mg de fer par gramme de la composition, provenant d'une ou plusieurs sources de fer, dans laquelle au moins une source de fer est un complexe d'acide aminé ;
    0,0 à 99 % d'un nutriment, le nutriment étant avantageusement choisi parmi les minéraux, les vitamines, les huiles oméga-3, oméga-6, oméga-9, végétales et leurs dérivés, le lycopène, la lutéine, la carnitine, la créatine, les extraits végétaux, les acides aminés, les peptides, les protéines et leurs mélanges en n'importe quelles proportions ;
    0,001 à 99 % d'un véhicule inerte acceptable du point de vue pharmaceutique ou nutritionnel ;
    0,0 à 99 % d'un édulcorant, l'édulcorant étant avantageusement choisi parmi le saccharose, le sorbitol, le xylitol, le fructose, le glucose, le sucralose, l'aspartame, l'acésulfame potassique, la saccharine sodique, le cyclamate, la thaumatine, les stéviosides, les rébaudiosides, le néohespéridine dihydrochalcone, l'alitame et leurs mélanges en n'importe quelles proportions ;
    0,001 à 20 % d'agents aromatisants ;
    0,001 à 1 % d'additifs colorants ;
    0,0 à 20 % et de préférence 0,01 à 5 % d'au moins un additif choisi parmi les siccatifs, les hydratants, les antioxydants, les épaississants, les stabilisants, les séquestrants, les lubrifiants, les conservateurs et les régulateurs d'acidité, ainsi que leurs combinaisons.
  12. Composition selon la revendication 10, comprenant au moins deux sources de fer, la deuxième source de fer étant avantageusement choisie parmi le citrate ferreux, le citrate ferrique, le tartrate ferreux, le tartrate ferrique, les citrates et tartrates de fer et de sodium, l'hypophosphite ferrique, l'albuminate ferrique, le chlorure ferrique, le chlorure ferreux, le sulfate ferrique, le sulfate ferreux, le sulfate d'ammonium ferrique, le sulfate d'ammonium ferreux, le citrate ferrique, le citrate d'ammonium ferrique, le gluconate ferreux, l'iodure ferreux, le lactate ferreux, le fumarate ferreux, le triglycinate ferrique, le bisglycinate ferreux, l'aspartate-glycinate ferreux, le nitrate ferrique, l'aspartate ferrique, le phosphate ferrique, l'hydroxyde ferreux, l'hydroxyde ferrique, l'oxyde ferreux, l'oxyde ferrique, le fer métallique, l'ascorbate ferrique, le formiate ferreux, l'acétate ferreux, le malate ferreux, le glutamate ferreux, le sulfate de glycine et de fer et le pyrophosphate ferrique soluble, le sous-sulfate ferrique, le citrate de sodium ferrique, l'édétate de sodium et de fer, le formiate ferrique, l'oxalate d'ammonium ferrique, l'oxalate de potassium ferrique, l'oxalate de sodium ferrique, le peptonate ferrique, et leurs mélanges en n'importe quelles proportions.
  13. Composition selon la revendication 10, qui est sous la forme d'une solution aqueuse et qui comprend :
    0,01 à 12 % de fer(III) ;
    0,01 à 30 % d'un acide organique, l'acide organique étant avantageusement choisi parmi les acides citrique, oxalique, tartrique, malique, succinique, adipique, lactique, glycolique, ascorbique, acétique, salicylique, maléique, malonique, fumarique, la pectine, les hydrolysats de pectine, et leurs mélanges, et de préférence l'acide citrique ;
    0,5 à 70 % d'un acide aminé, l'acide aminé étant avantageusement choisi parmi la glycine, la L-lysine, la L-alanine, la L-phénylalanine, la L-leucine, la L-isoleucine, la L-proline, la L-hydroxyproline, la L-arginine, la L-ornithine, la L-méthionine, l'acide L-aspartique, l'acide L-glutamique, la L-valine, la L-thréonine, la L-isothréonine, la L-histidine, le L-tryptophane, la L-sérine, la L-glutamine, la L-citrulline, et aussi leurs mélanges et leurs formes énantiomorphes, et de préférence la glycine ;
    0,01 à 25 % d'un cation, le cation étant avantageusement choisi parmi le sodium, le potassium, le calcium, le magnésium et l'ammonium, et de préférence le sodium ;
    40 à 99,9 % d'eau.
  14. Composition selon la revendication 10, comprenant en outre :
    0,001 à 99 % d'un nutriment, le nutriment étant avantageusement choisi parmi les minéraux, les vitamines, les huiles oméga-3, oméga-6, oméga-9, végétales et leurs dérivés, le lycopène, la lutéine, la carnitine, la créatine, les extraits végétaux, les acides aminés, les peptides, les protéines et leurs mélanges en n'importe quelles proportions ;
    0,001 à 99 % d'un édulcorant, l'édulcorant étant avantageusement choisi parmi le saccharose, le sorbitol, le xylitol, le fructose, le glucose, le sucralose, l'aspartame, l'acésulfame potassique, la saccharine sodique, le cyclamate, la thaumatine, les stéviosides, les rébaudiosides, le néohespéridine dihydrochalcone, l'alitame et leurs mélanges en n'importe quelles proportions ;
    0,001 à 20 % d'agents aromatisants ;
    0,001 à 1 % d'additifs colorants ;
    0,0 à 20 % et de préférence 0,01 à 5 % d'au moins un additif choisi parmi les siccatifs, les hydratants, les antioxydants, les épaississants, les stabilisants, les séquestrants, les lubrifiants, les conservateurs et les régulateurs d'acidité, ainsi que leurs combinaisons.
  15. Composé selon les revendications 1 et 2 ou composition selon les revendications 10 à 14 pour une utilisation en tant que médicament, substance pharmaceutique ou complément nutritionnel, avantageusement pour prévenir et/ou traiter des insuffisances en fer chez des humains et des animaux.
EP15856332.0A 2014-11-07 2015-11-05 Composés d'acides aminés de fer, procédé de préparation de composés d'acides aminés de fer, compositions contenant des composés d'acides aminés de fer et leurs utilisations Active EP3216782B1 (fr)

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WO2017167963A1 (fr) * 2016-03-31 2017-10-05 Medical Research Council Procédés de production de compositions de maltol ferrique à partir d'un hydroxyde ferrique modifié par un ligand et d'un hydroxyde ferrique recouvert d'un ligand
US20200129544A1 (en) * 2017-06-30 2020-04-30 Rozegen Llc Iron glycine sulfate compositions and uses thereof
CN112203639A (zh) * 2018-05-16 2021-01-08 法国诗华大药厂 兽医学组合物和其用于控制非人类哺乳动物的铁缺乏的用途
IT201800006414A1 (it) * 2018-06-19 2019-12-19 PREPARATI PER LA CORREZIONE DEL pH E PRODUZIONE DI IDROGENO MOLECOLARE E LORO UTILIZZO NEGLI ALIMENTI E BEVANDE
CA3118750C (fr) * 2018-11-30 2023-08-01 Balchem Corporation Compositions de complexes metalliques ou chelates metalliques comprenant des nanoparticules minimales
EP3890779A4 (fr) * 2018-12-07 2022-08-17 University of Florida Research Foundation, Incorporated Compositions améliorant l'absorption du fer et leurs procédés d'utilisation
CN109770299A (zh) * 2019-02-28 2019-05-21 四川李记乐宝食品有限公司 一种脆爽泡豇豆及其制备方法
CN114945551B (zh) * 2019-12-20 2023-03-24 约斯特化学公司 柠檬酸甘氨酸镁共盐
WO2021153199A1 (fr) * 2020-01-31 2021-08-05 太陽化学株式会社 Composition contenant du fer
WO2021254699A1 (fr) * 2020-06-19 2021-12-23 Unilever Ip Holdings B.V. Boisson à base de thé enrichie en fer
CN113100440B (zh) * 2021-02-28 2023-07-21 韩长平 一种纳米有机硒及其制备方法
CN114010618B (zh) * 2021-11-16 2023-10-27 吉林大学 一种在水溶液中制备的铁/寡肽复合物包覆的羟基氧化铁纳米梭及其制备方法
ES2990173B2 (es) * 2023-05-26 2025-04-08 Fund Gaiker Complejo de inclusion cuaternario de hidroxitirosol, triptofano, arginina y gluconato de zinc, metodo de obtencion y uso
CN119699474A (zh) * 2023-09-28 2025-03-28 安砝技术有限公司 柠檬酸铁铵有机酸复合物及其制备方法和应用

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EP3216782A4 (fr) 2018-07-18
WO2016070257A1 (fr) 2016-05-12
US10913705B2 (en) 2021-02-09
US20180370903A1 (en) 2018-12-27
US20210122705A1 (en) 2021-04-29
EP3216782A1 (fr) 2017-09-13

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